Efficacy of mFOLFOX7 regimen systemic chemotherapy combined with camrelizumab and apatinib for hepatocellular carcinoma with Vp4 portal vain tumor thrombus / 中华消化外科杂志

Objective:To investigate the efficacy of mFOLFOX7 regimen systemic chemo-therapy combined with camrelizumab and apatinib for hepatocellular carcinoma (HCC) with Vp4 portal vain tumor thrombus (PVTT).Methods:The single-arm, open, exploratory clinical study was conducted. The clinicopathological data of 15 HCC patients with Vp4 PVTT who were admitted to the Sun Yat-sen Memorial Hospital of Sun Yat-sen University from April 2021 to October 2023 were collected. There were 14 males and 1 female, aged 48(range, 33-67)years. All patients underwent treatment with mFOLFOX7 regimen combined with camrelizumab and apatinib. Observa-tion indicators: (1) clinical efficacy; (2) survival of patients. Measurement data with skewed distribution were represented as M(rang), and count data were described as absolute numbers or percentages. Results:(1) Clinical efficacy. All 15 patients underwent treatment with mFOLFOX7 regimen combined with camrelizumab and apatinib. According to the response evaluation criteria in solid tumors version 1.1, the ratio of objective response, ratio of complete response, ratio of partial response, ratio of disease control, median progression free survival time and median total survival time of the 15 patients were 10/15, 1/15, 9/15, 15/15, not reached and not reached. The median progression free survival time and median total survival time were both >9 months. According to the modified response evaluation criteria in solid tumors, the ratio of objective response, ratio of complete response, ratio of partial response, ratio of disease control, median progression free survival time and median total survival time of the 15 patients were 12/15, 6/15, 6/15, 15/15, not reached and not reached. The median progression free survival time and median total survival time were both >9 months. Of the 15 patients, 7 cases were successfully treated with conversion therapy with the surgical conversion rate as 7/15, and all of them achieved R 0 resection. The other 6 cases were failed in conversion therapy, and there were 2 cases still undergoing conversion therapy. Of the 7 patients with successful conver-sion therapy, 5 cases achieved complete pathological remission, 1 case achieved major pathological remission with 90% of tumor tissue necrosis, and 1 case achieved complete remission through imaging examination, but new liver lesions appeared in multiple locations during further observation which were surgically removed. Results of histopathology examination on the patient confirmed multiple liver metastases. The proportion of treatment-associated adverse reactions in 15 patients was 13/15, with 7/15 having ≥grade 3 adverse reactions, including diarrhea (3/15), neutropenia (2/15), thrombo-cytopenia (2/15), and elevated aspartate aminotransferase (2/15). One patient may experience ≥1 adverse reaction. All patients were improved after symptomatic treatment. (2) Survival of patients. All 15 patients were followed up for 13.0(range, 2.0-31.0)months. During the follow-up period, 3 patients died. One case died of upper gastrointestinal bleeding after achieving partial remission, with a survival time of 7.5 months. One case died of multiple liver metastases of tumor, with tumors accounting for over 70% volume of liver and a survival time of 9.5 months. One case with multiple liver tumors and bilateral lung metastasis died due to disease progression after achieving partial remission, with a survival time of 13.5 months. The postoperative follow-up time for 7 patients undergoing surgical treatment was 14.0(range, 2.0-25.0)months. Of the 7 patients, 1 case experien-ced tumor recurrence 20.0 months after surgery, and 6 cases had no recurrence at last time of the follow-up (3 cases completed treatment and entered follow-up observation). The longest survival time was 31.0 months. Conclusion:The mFOLFOX7 regimen systemic chemotherapy combined with camrelizumab and apatinib for HCC with Vp4 PVTT is safe and feasible.

Construction and analysis of a predictive model for chemotherapy response of patients with colorectal cancer based on tissue chip technology / 中华内分泌外科杂志

Objective:To explore the prediction model of tissue chip technology for the chemotherapy response of patients with colorectal cancer.Methods:217 patients with colorectal cancer who had received standardized chemotherapy in the Affiliated People’s Hospital of Ningbo University from Jan. 2017 to Dec. 2019 were prospectively selected. The patients were randomly divided into training set (152 cases) and test set (65 cases) according to the ratio of 7:3, and were followed up for 6 months. The clinical data of the patients in the training set were compared, the expression levels of Ang-2, caspase-3 and CD147 in the patients were analyzed by tissue microarray technology, and the related factors affecting the responsiveness of colorectal cancer chemotherapy were analyzed by the Logistic regression model. R software was used based on the training set. A nomogram prediction model was built and model performance on the test set was evaluated.Results:One case was excluded from the training center, and 151 cases were finally included, including 93 cases in the chemotherapy response group and 58 cases in the chemotherapy response group. The tumor diameter, serum carcinoembryonic antigen, caspase3, Ang2 expression level, and the proportion of clinical stage IV in the poor chemotherapy group were significantly higher than those in the good chemotherapy group (all P<0.05) ; Logistic regression showed tumor diameter ( OR=2.394), serum carcinoembryonic antigen ( OR=1.878), caspase-3 ( OR=4.261), Ang-2 expression level ( OR=5.457), and clinical stage IV ( OR=5.954) were independent risk factors for adverse drug reactions in patients with colorectal cancer (all P<0.05). The consistency index (C-index) for predicting the factors related to adverse chemotherapy reactions in patients with colorectal cancer was 0.915. External verification showed that the sensitivity was 86.96%, the specificity was 92.50%, and the accuracy was 90.48% (42/65) . Conclusion:The expression levels of Ang-2 and caspase-3 are correlated with the responsiveness of colorectal cancer to chemotherapy, and can be used as predictive indicators to evaluate the responsiveness of colorectal cancer to chemotherapy.

Pharmacokinetics of sugammadex in reversal of rocuronium-induced muscle relaxant residual in infants and young children undergoing daytime surgery / 中华麻醉学杂志

Objective:To investigate the pharmacokinetics of sugammadex in reversal of rocuronium-induced muscle relaxant residual in infants and young children undergoing daytime surgery.Methods:One hundred and four pediatric patients of either sex, aged 3-36 months, of American Society of Anesthesiologists Physical Status classification Ⅱ, with body mass index of 18.5-28.0 kg/m 2, diagnosed with oblique inguinal hernia and/or hydrocele, scheduled for laparoscopic high ligation of hernia sac and/or high ligation of sphingoid surgery, were included in the study. Intraoperative neuromuscle relaxation was assessed by transdermal stimulation of the ulnar nerve in the wrist using a TOF Guard monitor. Rocuronium 0.9 mg/kg, propofol 3 mg/kg, and sufentanyl 0.5 μg/kg were intravenously injected for anesthesia induction, and propofol 6-8 mg·kg -1·h -1 was intravenously infused to maintain anesthesia. The pediatric patients were divided into Ⅰgroup and Ⅱ group according to the degree of postoperative neuromuscular block. In group Ⅰ, sugammadex 2 mg/kg was intravenously injected when TOF returned to T 2 recurrence. In group Ⅱ, sugammadex 4 mg/kg was intravenously injected when the single stimulation count was 1 or 2 after tetanic stimulation. At 2 and 10 min after rocuronium administration, at the end of operation, 2 and 10 min after sugammadex administration, and when the children met the standard of leaving the resuscitation room, venous blood samples were collected for determination of plasma concentrations of rocuronium and sugammadex using ultra-high performance liquid chromatography-mass spectrometry. Pharmacokinetic parameters were determined using the Pheonix WinNonlin software. The onset of rocuronium and time for recovery of TOF ratio to 90% were recorded. Results:The pharmacokinetics of sugammadex was fitted to the nonlinear mixed-effect satrioventricular model.There was no significant difference in the peak concentration, area under the drug concentration-time curve, elimination half-life, apparent clearance, apparent volume of distribution, mean retention time, and time for TOF ratio returning to 90% between the two groups ( P> 0.05). Conclusions:The pharmacokinetics of sugammadex in reversal of rocuronium-induced muscle relaxant residual is fitted to a nonlinear mixed-effect satrioventricular model, and sugammadex 2 and 4 mg/kg have similar pharmacokinetics in infants and young children undergoing daytime surgery.

Establishment of cell models for PXR, FXR and LXRαagonists high-throughput screening based on reporter gene assay / 中国药理学通报

Aim To develop an in vitro high throughput drug screening system based on reporter gene assay for identification of novel compounds with PXR, FXR and LXRα agonist activity. Methods The expressions of exogenous PXR, FXR and LXRαgene in HEK293, HepG2 and LS174T cells were examined by Real-Time quantity PCR. pSG5-hPXR and pGL3-XREM-CYP3A4, pEGFP-N3-hFXR and EcRE-TK-Luc, pCMX-FLAG-hLXRα and pGL3-XREM-CYP3A4 were cotransfected into cells and the optimal ratio of three plasmids was determined. The dose-response relationship between the positive drug and the fold induction was determined. The specificity of the model was ex-amined, and the repeatability was also determined by Z′ value. Results ① The PXR, FXR and LXRα mRNA expression in HEK293 cell is low among three different cells. ②reporter gene vector and expression plasmid ratio of 1∶ 1, 2∶ 1 and 2∶ 1 were proved to be suitable for highest relative luciferase activity for PXR, FXR or LXRα agonist screening model. ③ The relative luciferase activity was induced by Rif, CDCA or T0901317 in a dose-dependent manner. ④Only Rif, CDCA or T0901317 could significantly increase the relative luciferase activity in PXR,FXR or LXRα agonist screening model, no effect of other nuclear re-ceptors agonist was observed, and the values of Z′-factor for PXR, FXR and LXRαagonist screening model were 0. 58, 0. 66 and 0. 63, respectively. Conclusion An in vitro PXR, FXR and LXRα agonist high-throughput screening models are devel-oped with acceptable specificity and repeatability, and the mod-els can be used to screen PXR, FXR and LXRα agonist.

Significance of micro RNA-21 expression in diffuse large B-cell lymphoma / 白血病·淋巴瘤

ObjectiveTo investigate the expression of miR-21 in diffuse large B cell lymphoma (DLBCL)and normal lymph tissues and its potential relevance with clinicopathological characteristics.MethodsThe expression levels of miR-21 in 50 primary DLBCL and 12 normal lymph node tissue specimens were examined by TaqMan real-time polymerase chain reaction.The expression of bcl-2 and p53 was detected by immunohistochemistry staining. ResultsThe expression of miR-21 was significantly higher in tumor tissues than that in normal tissues, in GCB subtypes higher than in non-GCB subtypes. And it was negatively correlated with bcl-2(P=0.020),while positively correlated with p53(P=0.022). Up-regulated miR-21 expression was low in three years of survival rate. ConclusionMiR-21 may indicate a more aggressive phenotype and serve as a molecular prognostic marker in DLBCL. High-expression of miR-21 is a key feature that is correlated with cell proliferation in DLBCL.miR-21 may have some guiding significance in prognosis.bcl-2,p53 is possibly one of the targets of miR-21 in DLBCL.

Development and application of HPLC method in simultaneous determination of mycophenolic acid and its 7-O-glucuronide metabolite in human plasma / 中国基层医药

Objective To establish a high-performance liquid chromatography method for simultaneous determination of mycophenolic acid(MPA) and its 7-O-glucuronide metabolite (MPAG) in human plasma and to study pharmacokinetics of MPA in Chinese renal transplant recipients after administration of mycophenolate mofetil( MMF). Methods Plasma protein was precipitated with metlianol: 5% ZnSO4 ( 70∶30, V∶ V), using naproxen as internal MPA and MPAG after 1.5g/d administration of MMF in 6 early-stage renal transplant recipients were as follows :Tmax was(1.08±0.74)h and(2.58±1.24)h,Cmax was(21.33±8.61)mg/L and(106.98±31.91)mg/L,AUCO-t was (58.73 ±16.26)mg ? L-1 ? h-1 and(833.32±215.03)mg ? L-1 ? h-1,respectively.Conclusion This method was accurate, sensitive and specific and it was successfully applied in therapeutic drug monitoring (TDM) of mycophenolate mofetil in early-stage renal transplant recipients.

A study on the expression of erbB4/HER4 and VEGF in NSCLC / 中国医师杂志

Objectives To explore the expression of HER4 and VEGF in NSCLC and elucidate the relationship between their expression and the characteristic of clinical pathology. Methods 82 cases of paraffin-embedded tissues from informative NSCLC were used to detect the expression of HER4 and VEGF by means of immunohistochemical assay. Results HER4 is overexpressed in 65;9%of NSCLC cases. The overexpression of HER4 is correlated with the lymph node metastasis and TNM staging. VEGF is expressed in 53.7%of NSCLC cases. The expression of VEGF is also correlated with the lymph node metastasis and TNM staging, and the expression of VEGF is correlated with the overexpression of HER4.Conclusions HER4 and VEGF are the protein to regulate the growth of NSCLC and it might be a good way for the treatment of NSCLC by suppressing the overexpression of HER4 and VEGF.

Study on Pharmacokinetics and Bioavailability of Ranitidine Hydrochloride Capsule in Human Body / 中国药房

OBJECTIVE:To study the pharmacokinetics and bioequivalence of both domestic ranitidine hydrochloride capsules and imported ranitidine hydrochloride tablets.METHODS:20healthy volunteers were randomized into groups,whose plasma concentrations of ranitidine were determined at different time after single oral dose of300mg ranitidine hydrochloride capsule or ranitidine hydrochloride tablets300mg by own control by a RP-HPLC method,the pharmacokinetic parameters were computed and which were experienced variance analysis and two-way t-tests and one-way t-tests.RESULTS:The respective pharmacokinetic parameters of ranitidine hydrochloride tablets and ranitidine hydrochloride capsuless were as fol?lows,the C max were(1247.1?547.5)?g/L and(1294.8?613.2)?g/L;t max were(2.98?0.73)h and(2.73?0.80)h;t 1/2 were(3.17?0.36)h and(3.33?0.42)h;AUC 0～t were(5805.9?1403.5)(?g?h)/L and(5941.2?1526.3)(?g?h)/L;AUC 0～∞ were(6163.8?1456.4)(?g?h)/L and(6351.8?1652.7)(?g?h)/L;The relative bioavailability of the ranitidine hydrochloride capsules to ranitidine hydrochloride tablets was(104.3?24.3)%.CONCLUSION:Ranitidine hydrochloride capsules and the ranitidine hydrochloride tablets were bioequivalent.

A case study of leukemia with irregular anti-Ce IgG antibody / 北京大学学报(医学版)

When we did compatibility testing, we found a case of leukemia with irregular antibody. The antibody specificity was identified as anti-Ce using panel-cell, and was IgG antibody. The anti-Ce antibody had both anti-C and anti-e activity. It is very difficult to find a Ce antigen negative blood for transfusion. The compatible donors rate is very low, only 2%-3%.

Clinicopathological analysis and genetic diagnosis of subcutaneous panniculitic T-cell lymphoma / 临床与实验病理学杂志

Purpose　To explore the clinicopathological features of subcutaneous panniculitic T-cell lymphoma(SPTCL) and significances of genetic analysis in the diagnosis. Methods　Histopathology, immunohistochemitry and detection of clonal gene rearrangement by PCR were used in 3 cases of subcutaneous panniculitic T-cell lymphoma (SPTCL), which were originally diagnosed as relapsing nodular nonsuppurative panniculitis. Results　Three misdiagnostic cases were correctly redefined as subcutaneous panniculitic T-cell lymphoma, with immunophenotype of CD45+,CD45RO+, Mac387－,and clonal TCR-β gene rearrangement. Conclusions　Subcutaneous panniculitic T-cell lymphoma has distinctive clinicopathological features. Genetic analysis is an effective method for the diagnosis of SPTCL.

Pharmacokinetics and Bioavailability of Two Kinds of Famotidine Capsule in Healthy Volunteers / 中国药房

OBJECTIVE:To study the pharmacokinetics of two kinds of famotidine capsule from different factories in healthy volunteers and to evaluate the bioavailability of them METHODS:A single oral 40 mg dose of famotidine capsule of reference or test preparation was given to healthy male volunteers according to an open randomized crossover study The plasma concentrations of famotidine were determined by a RP-HPLC method The pharmacokinetic parameters and bioavailability of test preparation were compared with reference preparation RESULTS:The main pharmacokinetic parameters of the reference preparation and the test preparation were as follows:Cmax were(189 9?72 1)?g/L and(170 1?59 6)?g/L;Tmax were(2 5?0 8)h and (2 1?0 8)h;T1/2 were(4 1?0 9)h and(3 8?0 8)h;AUC0～t were (1 031 7?316 7)?g/(L?h)and(1 019 4?290 5)?g/(L?h);AUC0→∞ were(1 123 9?346 0)?g/(L?h)and(1 103 4?312 0)?g/(L?h);The relative bioavailability of reference to test preparation was(101 6?22 6)% CONCLUSION:The results showed that the reference preparation and the test preparation were bioequivalent